Research Description
My general research interests lie in developing computational models that couple biochemical signaling and mechanics in biological cells. I am currently a postdoctoral researcher in the Rangamani Lab at UCSD, where I led development of a software framework for running spatial simulations of cell signaling in realistic cellular geometries (see more on this framework, SMART, below). I have applied such approaches to develop predictive models of mechanotransduction signaling in mammalian cells, in particular to understand the response of cells to nanotopography. My previous work in UC Davis in the Heinrich Lab examined the role of calcium bursts in human neutrophil chemotaxis (chasing after pathogens) and phagocytosis (consuming pathogens). Read below for more information, and see my publications page for a full list of papers.
Postdoctoral Research
UC San Diego Pharmacology, Rangamani Lab
Predictive modeling of cellular mechanotransduction
My recent research has largely centered on mechanistic models of cellular mechanotransduction, with a particular focus on YAP/TAZ signaling. Building from foundational models for YAP/TAZ mechanotransduction in well-mixed (Sun et al 2016) and spatial frameworks (pioneered by our lab in collaboration with Prof. Stephanie Fraley - Scott et al 2021), I have added biochemical details and spatial details across several projects. My first study considered a well-mixed framework, examining the coupling between mechanotransduction and circadian oscillations (Francis and Rangamani, 2024). I then moved primarily to spatial simulations, using our software package SMART (detailed below). As an ongoing collaboration with Prof. Zeinab Jahed’s research group in UCSD Nanoengineering, I have developed models that predict cellular mechanoresponse to the topography of their environment. These models are informed and tested by experiments with cells on arrays of nanopillars (example simulation shown here). Our initial joint publication focused on the effects of nanoscale plasma membrane curvature induced by nanopillars and stretch/rupture of the nuclear envelope on the transport of YAP/TAZ into the nucleus (Francis and Sarikhani et al 2025). Our recent preprint builds from this work to more broadly investigate the role of nuclear mechanics in cell mechanoresponse to nanotopography. This study (Francis et al 2026, bioRxiv) shows that nanoscale substrate curvature induces remodeling of the nuclear lamina, which is composed of nucleoskeletal filaments known as lamins. This has implications for YAP/TAZ transport, and more broadly for the likelihood of nuclear envelope rupture in different environments.
Spatial Modeling Algorithms for Reactions and Transport (SMART)
Cell signaling networks are traditionally modeled by assuming that intracellular regions are well-mixed, leading to a network of ordinary differential equations. However, we know that cell )signaling is a fundamentally spatial process, with influxes of molecules occurring at specific regions of the plasma membrane and advection or diffusion determining the distribution of molecules within the cell. Overall, this creates a complicated system of equations, where certain molecules are confined to surfaces (membranes) within the cell, and others can diffuse within and between different volumetric compartments (e.g. the cytosol versus the nucleus). Building from software originally developed by former graduate student Dr. Justin Laughlin in the lab, I led the development of Spatial Modeling Algorithms for Reactions and Transport (SMART), which allows users to specify details about the molecular species, reactions, parameters, and compartments involved in a given cellular reaction network, then assemble these into a system of equations that can be readily solved using the finite element method via the FEniCS software package. This was a collaboration with Simula Research Laboratory (specifically, Drs. Marie Rognes, Jørgen Dokken, and Henrik Finsberg) and with Prof. Chris Lee (UCSD Molecular Biology). A particular strength of SMART is its adaptability to complicated realistic cellular geometries, as shown in the video on the right (ATP generation within a detailed mitochondrion geometry from electron microscopy). We continue to develop SMART, with new features supporting both diffusion and advection in deforming cell geometries.
Computational modeling of store-operated calcium entry in skeletal muscle
UC San Diego, Rangamani Lab
In August 2022, I joined Dr. Padmini Rangamani’s group at UC San Diego as a postdoctoral scholar and began developing a computational model to explore the role of store-operated calcium fluxes in skeletal muscle fiber contractility. Store-operated calcium entry (SOCE) is the process by which depletion of intracellular calcium stores (such as the sarcoplasmic reticulum in this case) lead to opening of calcium channels in the cell membrane, allowing for store refilling. Given the large calcium release events that occur frequently upon muscle activation and facilitate contraction, we hypothesized that SOCE is important for sustaining high levels of force in muscle fibers. This was supported by some experimental studies in the literature, but had not been systematically investigated using mathematical modeling.
In the course of this project, I mentored one masters student, Anusha Kumar, who worked on developing this model and wrote her masters thesis on her findings. I then mentored an undergraduate research, Juliette Hamid, whose dedicated efforts allowed us to simulate not just calcium dynamics, but also the dynamics of force and ATP hydrolysis over time. Our collective efforts demonstrated that the role of SOCE is in fact context-dependent; although SOCE enhances force production and mitigates fatigue in certain cases of extended exercise, in certain cases it does not help at all, or can even worsen the effects of fatigue. The work will be released in Journal of Physiology in the near future, with a preliminary version found on bioRxiv.
Check out all the videos below and more at the Heinrich Lab YouTube page
PhD Dissertation: Calcium bursts and mechanics in human neutrophil chemotaxis and phagocytosis
UC Davis, Heinrich Lab
Close-up view of a calcium burst in a human neutrophil during phagocytosis.
In my dissertation research, I first examined the mechanical underpinnings of human neutrophil phagocytosis, the process by which immune cells consume pathogens such as bacteria or fungi. I specifically examined the process of cell spreading during frustrated phagocytosis, a case in which the target is too large for the cell to completely consume. In collaboration with talented undergraduate researchers in our lab, Hugh Xiao and Lay Heng Teng, I experimentally probed the effects of ligand density on phagocytic spreading. We coated glass surfaces with different densities of antibodies (molecules from the bloodstream that label pathogens as “the enemy”) and showed that the speed of spreading is similar across many different densities of IgG antibody. I developed a computational model of immune cell spreading, which revealed that this spreading process must be driven by active forces within the cell.
The second portion of my dissertation focused on the role of calcium bursts in neutrophil chemotaxis and phagocytosis.
Undergraduate Research: Studying adhesion-free neutrophil chemotaxis
UC Davis, Heinrich Lab
No calcium bursts occur during chemotaxis
Chemotaxis is traditionally studied in conjunction with cell adhesion to surfaces. While this is obviously physiologically relevant, the cell is receiving multiple inputs in parallel: adhesive cues from the surface, as well as stimulus from the chemoattractant(s) being considered. In our dual micropipette manipulation system, we hold the cell off a surface to observe “pure” chemotaxis in which the chemoattractants should provide the only relevant stimulus. This proved invaluable in two separate research endeavors.
Neutrophil chemotaxis neither causes nor requires calcium bursts (first video on the right). I gave a presentation on this topic in 2016 at my first Biophysical Society Annual Meeting (I’ve been every year since as well!) We then published this work in 2018 in Science Signaling!
Pure chemotaxis experiments allow us to measure the relationship between particle size and maximum distance at which a neutrophil responds (lower video on the right). We published a letter in Biophysical Journal in which we presented the experimental side of this, supported by a theoretical paper in Frontiers of Immunology.
Other projects
UC Davis, Heinrich Lab
In the Heinrich Lab, I have also assisted and led out in multiple other projects, working together with several talented undergraduate researchers.
Measuring the relationship between phagocytic efficiency and IgG surface concentration on microparticles using flow cytometry.
In collaboration with the Roijjakkers Lab at the University of Utrecht, undergraduate researcher Jonathan Brand (now a PhD student at UCLA) and myself have worked to explore the mechanics of C3b-mediated phagocytosis. Materials from the Roijjakkers Lab allowed us to coat particles and surfaces with the human complement component C3b in a controlled manner. Jonathan conducted a series of phagocytosis experiments with our dual micropipette setup to observe phagocytosis of beads coated in C3b, and I have recently explored the dynamics of frustrated phagocytic spreading on C3b surfaces. Look out for a paper soon!
Eosinophil phagocytosis: We are very interested in how the neutrophil’s “cousin” behaves during phagocytosis. Our previous experiments have revealed key differences between neutrophil phagocytosis and eosinophil phagocytosis; I’ve worked with Julie Zimmer, Yiting Chen, and currently Sahand Salari-Namin to systematically characterize eosinophil phagocytosis, manuscript in the works.